Functional Analysis of pRb2/pl30 Interaction with Cyclins1

The retinoblastoma (Rb) family consists of the tumor suppressor pRb and related proteins pl07 and pRb2/pl30. Ectopie expression of pRb and p 1117results in a growth arrest of sensitive cells in the G, phase of the cell cycle. We demonstrated here that the growth-suppressive properties of pRb2/pl30 were also specific for the G, phase. The A-, E-, and D-type cyclins as well as transcription factor E2F1 and the EIA viral oncoprotein were able to rescue the pRb2/pl30-mediated G, growth arrest in SAOS-2 cells. The rescue with cyclins A and E correlated with their physical interaction with pRb2/pl30, which surprisingly has been found to occur over all phases of the cell cycle. The phosphorylation status as well as the kinase activity associated with pRb2/pl30 dramatically increased near the G,-S-phase transition. This suggests that, like the other Rb family mem bers, pRb and p 107, the phosphorylation of pRb2/pl30 is controlled by the cell cycle machinery and that pRb2/pl30 may indeed be another key G,-S-phase regulator.